Chromatin structure implicated in activation of HIV-1 gene expression by ultraviolet light.
We have investigated the effects of different DNA-damaging agents on HIV-1 gene expression. We find that agents that produce "bulky" DNA lesions, similar to those induced by ultraviolet light (UV), all dramatically increase HIV-1 gene expression, whereas agents that produce primarily base damage and DNA breakage, such as ionizing radiation, have little or no effect. We show that these effects are independent of DNA synthesis per se and do not require DNA nucleotide excision repair. The drug novobiocin effectively prevents the UV activation process, consistent with the idea that a change in DNA chromatin structure may be required. We suggest that a transient decondensation of chromatin structure, an early step in DNA nucleotide excision repair but not in base excision repair, may be the triggering mechanism. The decondensation may allow the transcriptional machinery better access to the HIV-1 promoter region, thereby increasing gene expression.
Valerie
K
K
Department of Macromolecular Sciences, Smith Kline and French Laboratories, King of Prussia, PA 19406-0939.
Rosenberg
M
M
D002843:Chromatin / Q000382:microbiology / Q000502:physiology* / Q000528:radiation effects; D004249:DNA Damage; D004279:DNA, Viral / Q000096:biosynthesis; D015870:Gene Expression / Q000187:drug effects / Q000528:radiation effects*; D005814:Genes, Viral; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D006367:HeLa Cells; D006801:Humans; D009675:Novobiocin / Q000494:pharmacology; D014466:Ultraviolet Rays; D014775:Virus Activation / Q000235:genetics* / Q000528:radiation effects; D014965:X-Rays
D002843:Chromatin; D004279:DNA, Viral; D009675:Novobiocin